The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A
The broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how A...
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2025-07-01
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| author | Xuemeng Shi Shuaiwu Chen Mingyang Liu Yali Fan Xin Wen Jingyi Wang Xiaoling Li Huimin Liu Lin Mao Li Yu Yuxin Hu Jun Xu |
| author_facet | Xuemeng Shi Shuaiwu Chen Mingyang Liu Yali Fan Xin Wen Jingyi Wang Xiaoling Li Huimin Liu Lin Mao Li Yu Yuxin Hu Jun Xu |
| author_sort | Xuemeng Shi |
| collection | DOAJ |
| description | The broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how ABHD17A regulates the dynamic S-palmitoylation modification of IFITM1 remains unknown. Here, we demonstrated that ABHD17A physically interacts with IFITM1 and increases the S-palmitoylation level of IFITM1. Sequence alignment revealed that ABHD17A lacked the DHHC motif, which is capable of catalyzing the S-palmitoylation modification. Thus, we screened multiple candidate palmitoylating and depalmitoylating enzymes that may contribute to ABHD17A-induced upregulation of IFITM1 S-palmitoylation. The recently discovered depalmitoylase ABHD16A was significantly downregulated by ABHD17A, which counteracted the palmitate-removing reactions of ABHD16A on IFITM1 and subsequently upregulated the S-palmitoylation level and antiviral activity of IFITM1. Our work therefore elucidated the unconventional role of depalmitoylase ABHD17A in elevating the S-palmitoylation modification, expanded the biological functions of ABHD17A in innate immunity, and provided potential targets for viral disease therapy. |
| format | Article |
| id | doaj-art-5b33eda9eb794040b23de07fbcac4a2d |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
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| series | Biomolecules |
| spelling | doaj-art-5b33eda9eb794040b23de07fbcac4a2d2025-08-20T03:32:31ZengMDPI AGBiomolecules2218-273X2025-07-0115799210.3390/biom15070992The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16AXuemeng Shi0Shuaiwu Chen1Mingyang Liu2Yali Fan3Xin Wen4Jingyi Wang5Xiaoling Li6Huimin Liu7Lin Mao8Li Yu9Yuxin Hu10Jun Xu11College of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Life Science, Henan Agricultural University, Zhengzhou 450046, ChinaThe broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how ABHD17A regulates the dynamic S-palmitoylation modification of IFITM1 remains unknown. Here, we demonstrated that ABHD17A physically interacts with IFITM1 and increases the S-palmitoylation level of IFITM1. Sequence alignment revealed that ABHD17A lacked the DHHC motif, which is capable of catalyzing the S-palmitoylation modification. Thus, we screened multiple candidate palmitoylating and depalmitoylating enzymes that may contribute to ABHD17A-induced upregulation of IFITM1 S-palmitoylation. The recently discovered depalmitoylase ABHD16A was significantly downregulated by ABHD17A, which counteracted the palmitate-removing reactions of ABHD16A on IFITM1 and subsequently upregulated the S-palmitoylation level and antiviral activity of IFITM1. Our work therefore elucidated the unconventional role of depalmitoylase ABHD17A in elevating the S-palmitoylation modification, expanded the biological functions of ABHD17A in innate immunity, and provided potential targets for viral disease therapy.https://www.mdpi.com/2218-273X/15/7/992ABHD17AIFITMS-palmitoylationpost-translational modificationvirus infection |
| spellingShingle | Xuemeng Shi Shuaiwu Chen Mingyang Liu Yali Fan Xin Wen Jingyi Wang Xiaoling Li Huimin Liu Lin Mao Li Yu Yuxin Hu Jun Xu The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A Biomolecules ABHD17A IFITM S-palmitoylation post-translational modification virus infection |
| title | The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A |
| title_full | The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A |
| title_fullStr | The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A |
| title_full_unstemmed | The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A |
| title_short | The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A |
| title_sort | unconventional role of abhd17a in increasing the s palmitoylation and antiviral activity of ifitm1 by downregulating abhd16a |
| topic | ABHD17A IFITM S-palmitoylation post-translational modification virus infection |
| url | https://www.mdpi.com/2218-273X/15/7/992 |
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